摘要:

ObjectiveTo study HIV envelope glycoprotein (Env)-mediated entry using a sensitive fusion assay.Design and methodsCD4+ lymphocytes or T-cell lines were labelled with fluorescent cytoplasm or membrane markers. Fusion with Env-expressing adherent cells was monitored by observing dye transfer from CD4+ cells to Env cells.ResultsCell-cell fusion began 20–30 min after co-cultivation at 37°C. Pre-binding at 4°C was observed not to decrease the lag phase before fusion. Cells expressing envelope glycoproteins from non-syncytium-inducing (NSI) HIV strains showed dye transfer between two cells without progression to syncytia. A glycosylphosphatidylinositol anchored Env was found to be incapable of mediating membrane fusion, as measured either by lipid or cytoplasm contents mixing. Primary mouse cells expressing human CD4 and mouse 3T3 cells stably expressing both human CD4 and human CD26 did not support fusion with our Env-expressing cells.ConclusionsEnv-mediated cell-cell fusion is a relatively slow process, probably reflecting a multi-step process occurring after CD4 binding and requiring the trans-membrane domain of gp41. Env proteins are able to mediate cell-cell fusion at least under some experimental conditions, indicating that lack of a syncytia phenotype does not rule out the possibility of fusion occurring between only two or a few cells.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesCorrelation of lysis of autologous CD4+ target cells by cytotoxic lymphocytes from HIV-seropositive patients to target activation, viral replication, and major histocompatibility complex (MHC) restriction.DesignTwenty-two HIV-infected patients were evaluated for lysis of activated CD4+ cells, concurrent with measurement of proliferation of the target cells, and with viral replication.MethodsTitrated standard51Cr-release assays for specific effector-to-target cell recognition, blocking antibodies and cell depletion for cell characterization, incorporation of [3H]- thymidine for proliferation, and p24 antigen capture assays for viral replication.ResultsHIV-infected patients had cytotoxic lymphocytes capable of recognizing activated CD4+ target cells in a non-MHC-restricted manner. The lysis depended on the degree of target activation, and was independent of viral replication.ConclusionsThis cytolytic activity is unique to HIV-infected patients, and is suggestive of activation-induced cell death that may contribute to the progressive depletion of CD4+ lymphocytes during HIV pathogenesis.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo model the predictive value of viral load measurements in asymptomatic patients with HIV-1 infection, who have CD4 cell counts > 500 × 106/l and no prior antiretroviral therapy, when the time of seroconversion and the prior levels of viremia are unknown.DesignA mathematical model was constructed for the changes in HIV RNA load over time based on data from cohorts of HIV-infected patients followed since the time of seroconversion.MethodsFor different values of viral load, the time to progression to AIDS or an equivalent state [progression to AIDS equivalent (PAE)] was calculated using a wide range of estimates for the time since seroconversion and the rate of change of the viral load over time.ResultsIn the absence of antiretroviral treatment, patients with a viral load of 105copies/ml serum are at risk for PAE in less than 3 years (0–3 years) and patients with a viral load half a log higher are at risk in less than 1 year. In contrast, patients with a viral load of 104,5have at least 1.9 years and may have up to 8 years before risk of PAE. Patients with a viral load of 104RNA copies/ml have at least 2.8 years and may have up to 19 years before risk of PAE. The rate of change of the viral load was an important predictor of outcome; the time since seroconversion had only a minor effect.ConclusionsThe viral load in the plasma or serum has predictive value even if the time of seroconversion is unknown. The rate of change of viral load over time may also lie an important predictive factor. Serial measurements of viral load over time may provide therapeutic guidance.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo examince the impact ot continuous versus intermittent Fluconazole therapy on fungal colonization and fluconazole resistance in the oophaynx of HIV-infected patients.DesignCase-conrol study.SetingDuke University Adult Infectious Diseases clinic, A teriary referral center in North Carolina which provies care for 700 HIV-infected personsPatientsNineteen HIV-infected patients on daily continusous fluconazole for a minimum of 6 months and eleven HIV-infected patients on intermitent luconazole for a minimum of 6 months were matched by sex and CD4 Cell count to HIV-infected patients who had not received fluconazole in the preceding 6 months.Main oucome measuresFungal isolation an fluconazole susceptibility testing were performed on oral saline rinses from each patientResultsThe patients taking coninuous fluconazole were more likely than matched conrols to have had sterile mouth rinses (14 out of 19 versus five out of 19; P <0.001), and the yeasts that were isolated were more likely than matched conrols o be non-cCandida albicans species and to have minimum inhibitory concentrations (MIC) to fluconazole ≤16g/ml. None of these isolates were associated with sympoms. In conrast, none of the patients in the intermitent fluconazole group had sterile cultures. When this roup was compared o conrols, they were more likely to have had non-C. Albicans species, and C. Albicans isolates obtained had higher MIC o fluconazole.ConclusionsLong-term continuous therapy wih fluconazole may prevent the appearance of Candida in the oral civity. This finding may reduce recurrence rates and miht favorably impact on the clinical appearance of mucosal candidiasis wih resistant C. albicans.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo ascertain predictors of survival in HIV-infected tuberculosis (TB) patients.DesignRetrospective cohort study.SettingNew York City public hospital.PatientsFifty-four consecutive HIV-seropositive patients with newly diagnosed TB and no other AIDS-defining illnesses.Main outcome measuresCD4+ T-lymphocyte counts, completion of anti-TB therapy, repeat hospitalizations with TB, and survival.ResultsForty-five (84%) of the 54 patients died a median of 15 months after TB diagnosis (range, 1–80 months), five (9%) were alive after a median of 81 months (range, 75–84 months), and four (7%) were lost to follow-up after a median of 42 months (range, 30–66 months). In univariate analyses, disseminated TB, intrathoracic adenopathy, oral candidiasis and CD4 count depletion were each associated with decreased survival. In a multivariate analysis, CD4 count depletion was the only independent predictor of decreased survival. Repeat hospitalization with TB occurred in 10 out of 15 patients who did not complete anti-TB therapy compared with one out of 21 patients who completed anti-TB therapy (P< 0.001).ConclusionThe clinical presentation of TB and CD4 count at TB diagnosis are each predictive of survival in HIV-seropositive TB patients. The CD4 count is the only independent predictor of survival.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo evaluate the relationship of drug use with maternal HIV culture positivity at delivery and perinatal HIV transmission.DesignMulticenter prospective cohort study.SettingObstetric and pediatric clinics in five cities in the United States.ParticipantsFive hundred and thirty HIV-infected pregnant women and their infants.Main outcome measuresMultivariate logistic regression was used to evaluate the association of 'hard drug' use (one or more of the following: cocaine, heroin/opiates, methadone, injecting drug use) assessed by self-report and urine toxicology with positive maternal HIV culture at delivery and perinatal HIV transmission.ResultsForty-two per cent of women used hard drugs during pregnancy. Increased probability of a positive maternal delivery HIV culture was significantly associated with prenatal hard drug use [odds ratio (OR), 3.081 and maternal cocaine use (OR, 2.98) among HIV-infected women with > 29% CD4+ lymphocytes. After adjusting for maternal culture positivity at delivery, CD4+ lymphocyte percentage and gestational age, significantly greater transmission risk was observed with hard drug use among women with membrane rupture > 4 h.ConclusionsOn the basis of self-report and urine toxicology, overall maternal hard drug use and cocaine use in the WITS cohort were associated with maternal HIV culture positivity at delivery, and maternal hard drug use was associated with perinatal transmission.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo reveal a possible impairment of the plasminogen activator system in the pulmonary infections of AIDS patients.DesignTo test the plasminogen activator system functionality in alveolar macrophages and bronchoalveolar lavage fluid (BALF) in control subjects and AIDS patients. Procedures were designed to defect the presence of imbalance in plasminogen activator activity and to ascertain if this imbalance is due to a direct effect of the HIV virus on macrophages or to superimposed opportunistic infection.MethodsAlveolar macrophages obtained by bronchoalveolar lavage (BAL) were either lysed with Triton X-100 or cultured for 24 h. Plasminogen activators and plasminogen activator inhibitors (PAI) were measured by chromogenic substrate assay and binding to12l-urokinase followed by 10% sodium dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PACE), respectively.ResultsPlasminogen activator activity in BALF and in alveolar macrophages from AIDS patients was decreased. This reduction was independent of the presence of an infectious pulmonary process. In contrast, free PAI was increased in AIDS patients withPneumocystis cariniiinfection. This increase is possibly caused by a different glycosylated form of PAI-2.ConclusionsOur data support the view that the pulmonary fibrogenic response is in part secondary to an imbalance within the plasminogen activator system and provide the basis for clarifying the role of these alterations in the pathophysiology of AIDS-related pulmonary infections.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo evaluate the impact of an HIV risk-reduction program among injecting drug users (IDu)in Denver, Colorado.DesignA Trageted, community-level intervention study with multiple, time-phased, cross-sectional measurements assessin HIV high-risk Behaviors among IDU in intervention and comparison sites

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveIn Tanzania during the past 6 years reported tuberculosis (TB) cases have nearly doubled, with proportionately much greater increases in smear-negative and extrapulmonary cases compared with smear-positive cases. At the same time, HIV infection has become widespread throughout the country. This survey was undertaken in order to study the association of TB and HIV and to determine the impact of HIV on present and future TB cases in Tanzania.MethodsThe survey design provided for HIV testing of a representative country-wide sample of approximately one-sixth of all new and relapse cases registered between January 1991 and December 1993, with linkage to demographic, clinical and bacteriological data for these cases. HIV surveillance data were used for comparison purposes.ResultsA total of 6928 TB cases from all of the country's 20 mainland regions were tested. The overall HIV seroprevalence was 32%. Both crude and adjusted odds ratios (OR) for HIV infection were higher in women, those aged 25–44 years, urban residents, cases of smear-negative and extrapulmonary disease, and persons with a bacille Calmette-Guérin (BCG) vaccination scar. The age-and sex-adjusted relative risk for HIV infection in TB patients compared to blood donors in the same regions was 7.1 (95% confidence interval, 6.6–7.5), and was significantly higher among those aged 25–34 years. Of 3360 patients with bacteriological culture results 46% were culture-positive forMycobacterium tuberculosis.Drug susceptibility tests were performed on 1164 isolates with the overall rate of drug resistance of 6.2%. Rates of initial resistance were low in both HIV-positive (4%) and HIV-negative (5.8%) patients. Rates of acquired resistance were higher (19% overall) and did not vary significantly by HIV serostatus. Initial combined resistance to both isoniazid and rifampicin was uncommon (0.4%) as was monoresistance to rifampicin (0.3%).ConclusionsThe higher OR for women and young adults reflect the higher rates of HIV infection in those populations. The finding that smear-positive relapse cases were no more likely to have HIV infection than new smear-positive cases suggests that the treatment regimen for new cases is effective in HIV-associated TB. The low rates of both initial and acquired drug resistance in HIV-positive patients is further evidence of adequacy of treatment. The higher relative risk for HIV infection among patients aged 25–34 years suggests increased HIV-related TB transmission. Finally, it is estimated that approximately two-thirds of the increase in the rate of smear-positive tuberculosis in the country can be directly attributed to HIV infection.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo determine whether frontloading (i.e., syringe-mediated drug-sharing) is a risk factor for HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among injecting drug users (IDU).DesignCross-sectional study. Data on sociodemographic and behavioural characteristics were obtained by a standardized questionnaire. Serum samples were tested for seromarkers for HIV, HBV and HCV.Setting and participantsIDU were recruited at 'low-threshold' storefront agencies (out-of-treatment sample), and at a centre for long-term drug use treatment (in-treatment sample). Individuals were included in the study if they had injected drugs within the previous 3 months.Main outcome measuresSerological evidence for HIV, HBV, HCV exposure.ResultsOf all IDU (n = 324), 84% had ever practised frontloading with non-sterile injecting equipment, and 46% had done so more than 100 times; 32% had front-loaded during the 6 months prior to the interview. The crude seroprevalence rates for HIV, HBV and HCV increased with the overall frequency of frontloading, and reached 22, 71 and 94%, respectively, among IDU who had frontloaded more than 100 times. After controlling for confounding effects by logistic regression, having practised front-loading more than 100 times was significantly associated with HIV infection [adjusted prevalence odds ratio (POR) 3.5; 95% confidence interval (CI), 1.4–9], and HCV infection (adjusted POR, 5.4; 95% CI, 2.3–12), but not with HBV infection. Another independent risk factor for all three virus infections was needle-sharing in prison.ConclusionsIn communities where sterile injection equipment is readily available, and IDU have substantially reduced their overall levels of needle-sharing, the practice of frontloading appears to be a major risk factor for infections by blood-borne viruses among IDU. Prevention activities should specifically address this risk behaviour.

ISSN:0269-9370    

出版商:OVID    

年代:1996

数据来源: OVID